Rivaroxaban With or Without Aspirin in Patients with Heart Failure and Chronic Coronary or Peripheral Artery Disease: The COMPASS Trial

BACKGROUND:

Patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD) and history of heart failure (HF) are at high risk for major adverse cardiovascular events (MACE). We explored the effects of rivaroxaban with or without aspirin in these patients.

METHODS:

The COMPASS trial randomized 27,395 participants with chronic CAD or PAD to rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily, rivaroxaban 5 mg twice daily alone, or aspirin 100 mg alone. Patients with NYHA class III or IV HF or left ventricular ejection fraction (EF) <30% were excluded. The primary MACE outcome comprised cardiovascular death, stroke, or myocardial infarction, and the primary safety outcome was major bleeding using modified ISTH criteria. Investigators recorded a history of HF and EF at baseline, if available. We examined the effects of rivaroxaban on MACE and major bleeding in patients with or without a history of HF and an EF < or ≥40% at baseline.

RESULTS:

Of the 5902 participants (22%) with a history of HF, 4971 (84%) had EF recorded at baseline and 12% had EF <40%. Rivaroxaban and aspirin had similar relative MACE reduction compared with aspirin in participants with HF (5.5% versus 7.9%; HR 0.68, 95% CI 0.53-0.86) and those without HF (3.8% vs 4.7%, HR 0.79, 95% CI 0.68-0.93, p for interaction 0.28) but larger absolute risk reduction (ARR) in those with HF (HF ARR 2.4%, NNT=42 no HF ARR 1.0%, NNT=103). The primary MACE outcome was not statistically different between those with EF<40% [HR 0.88, 95% CI 0.55-1.42) and ≥40% (HR 0.81, 95% CI: 0.67-0.98), p for interaction 0.36]. The excess hazard for major bleeding was not different in participants with HF (2.5% vs 1.8%, HR 1.36, 95% CI 0.88-2.09) compared to those without HF (3.3% vs 1.9%, HR 1.79, 95% CI 1.45-2.21, p for interaction 0.26). There were no significant differences in the primary outcomes with rivaroxaban alone.

CONCLUSIONS:

In patients with chronic CAD or PAD and a history of mild or moderate HF, combination rivaroxaban and aspirin compared with aspirin alone produces similar relative but larger absolute benefits compared with those without HF.

CLINICAL TRIAL REGISTRATION:

Unique Identifier: NCT01776424 URL: https://clinicaltrials.gov.